Telomerase mutations and carcinogenesis

Abstract

A telomere is a specific structure of repetitive nucleotide sequences at the ends of the chromosomes, which protects the chromosomes from degradation or fusion. The telomere dysfunction can lead to various diseases, such as aging and cancer. Telomerase reverse transcriptase (TERT) is a catalytic subunit of telomerase which maintains the integrity of telomere. Recurrent mutations in TERT promoter -124 C>T and -146 C>T have been identified in multiple cancer types, including melanoma, glioblastomas, bladder cancer and hepatocellular carcinoma. These TERT promoter mutations are correlated with higher levels of TERT mRNA, protein and enzymatic activity, which are also associated with telomere length. These mutations are beneficial to recruiting transcription factor GA-binding protein (GABP) to activate TERT gene expression. There discoveries will provide a new biomarker for diagnosis and treatment of human cancers.